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Cuihua Wang Sofia Barluenga Girish K. Koripelly Jean-Gonzague Fontaine Ruihong Chen Jin-Chen Yu Xiaodong Shen John C. Chabala James V. Heck Allan Rubenstein Nicolas Winssinger 《Bioorganic & medicinal chemistry letters》2009,19(14):3836-3840
Pochoximes are potent inhibitors of heat shock protein 90 (HSP90) based on the radicicol pharmacophores. Herein we present a pharmacokinetics and pharmacodynamics evaluation of this compound series as well as a phosphate prodrug strategy to facilitate formulation and improve oral bioavailability. 相似文献
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Yunzhu Qian Yingying Zhang Bin Wei Mengshu Zhang Jianxin Yang Cuihua Leng Zili Ge Xingshun Xu Miao Sun 《Journal of genetics》2018,97(1):137-143
Cleidocranial dysplasia (CCD; OMIM: 119600) is a rare autosomal dominant skeletal dysplasia caused by RUNX2 gene mutations. The present study described a sporadic case with CCD. The clinical data of the proband with CCD was reported and genetic analysis was performed. The proband presented with typical CCD features including supernumerary impacted teeth, bilateral clavicle dysplasia, delayed closure of cranial sutures, and short stature; while his hands were normal. Sequencing analysis of the entire coding region of the RUNX2 gene revealed no pathogenic changes; however, copy-number analysis with the Affymetrix HD array found \(\sim \)500 kb genomic microdeletion. Real-time quantitative PCR validated this microdeletion in the 1–4 exons of the RUNX2 gene. The junction point of the breaking DNA was located in the directly oriented AluSz6 and AluSx repetitive elements, indicating that this microdeletion might be generated through an Alu–Alu mediated mechanism. In addition, this microdeletion existed in 21.8% of the asymptomatic mother’s peripheral blood cells, demonstrating that the mosaicism was not associated with CCD phenotypes. In summary, a pathogenic microdeletion in the RUNX2 gene located on chromosome 6 was responsible for CCD. 相似文献
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Anning Li Yue Wu Jenny Linnoila Benjamin Pulli Cuihua Wang Matthias Zeller Muhammad Ali Grant K. Lewandrowski Jinghui Li Benoit Tricot Edmund Keliher Gregory R. Wojtkiewicz Giulia Fulci Xiaoyuan Feng Bakhos A. Tannous Zhenwei Yao John W. Chen 《Cancer immunology, immunotherapy : CII》2016,65(12):1545-1554
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Wang C Ashton TD Gustafson A Bland ND Ochiana SO Campbell RK Pollastri MP 《Bioorganic & medicinal chemistry letters》2012,22(7):2579-2581
Parasitic diseases, such as African sleeping sickness, have a significant impact on the health and well-being in the poorest regions of the world. Pragmatic drug discovery efforts are needed to find new therapeutic agents. In this Letter we describe target repurposing efforts focused on trypanosomal phosphodiesterases. We outline the synthesis and biological evaluation of analogs of sildenafil (1), a human PDE5 inhibitor, for activities against trypanosomal PDEB1 (TbrPDEB1). We find that, while low potency analogs can be prepared, this chemical class is a sub-optimal starting point for further development of TbrPDE inhibitors. 相似文献
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The Spt4p subunit of yeast DSIF stimulates association of the Paf1 complex with elongating RNA polymerase II 下载免费PDF全文
The Paf1 complex (Paf1C) interacts with RNA polymerase II (Pol II) and promotes histone methylation of transcribed coding sequences, but the mechanism of Paf1C recruitment is unknown. We show that Paf1C is not recruited directly by the activator Gcn4p but is dependent on preinitiation complex assembly and Ser5 carboxy-terminal domain phosphorylation for optimal association with ARG1 coding sequences. Importantly, Spt4p is required for Paf1C occupancy at ARG1 (and other genes) and for Paf1C association with Ser5-phosphorylated Pol II in cell extracts, whereas Spt4p-Pol II association is independent of Paf1C. Since spt4Delta does not reduce levels of Pol II at ARG1, Ser5 phosphorylation, or Paf1C expression, it appears that Spt4p (or its partner in DSIF, Spt5p) provides a platform on Pol II for recruiting Paf1C following Ser5 phosphorylation and promoter clearance. spt4Delta reduces trimethylation of Lys4 on histone H3, demonstrating a new role for yeast DSIF in promoting a Paf1C-dependent function in elongation. 相似文献
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Liu C Kawata T Shigematsu N Cucinotta F George K Saito M Uno T Isobe K Ito H 《Radiation research》2010,174(5):566-573
Potentially lethal damage (PLD) and its repair were studied in confluent human fibroblasts by analyzing the kinetics of chromosome break rejoining and misrejoining in irradiated cells that were either held in noncycling G(0) phase or allowed to enter G(1) phase of the cell cycle immediately after 6 Gy irradiation. Virally mediated premature chromosome condensation (PCC) methods were combined with fluorescence in situ hybridization (FISH) to study chromosomal aberrations in interphase. Flow cytometry revealed that the vast majority of cells had not yet entered S phase 15 h after release from G(0). By this time some 95% of initially produced prematurely condensed chromosome breaks had rejoined, indicating that most repair processes occurred during G(1). The rejoining kinetics of prematurely condensed chromosome breaks was similar for each culture condition. However, under noncycling conditions misrepair peaked at 0.55 exchanges per cell, while under cycling conditions (G(1)) it peaked at 1.1 exchanges per cell. At 12 h postirradiation, complex-type exchanges were sevenfold more abundant for cycling cells (G(1)) than for noncycling cells (G(0)). Since most repair in G(0)/G(1) occurs via the non-homologous end-joining (NHEJ) process, increased PLD repair may result from improved cell cycle-specific rejoining fidelity of the NHEJ pathway. 相似文献
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Optimization of renewal regime for improvement of polysaccharides production from Porphyridium cruentum by uniform design 总被引:1,自引:0,他引:1
To probe the effects of renewal regime on the production of polysaccharides, Porphyridium cruentum was cultured semi-continuously in flat plate photobioreactor. Uniform design was used to optimize renewal conditions. Quadratic mathematic models related to productivity, total recovery yield of biomass and polysaccharides were set up to clarify the influence of individual factors and their interactions. According to the mathematic models, the optimal semi-continuous condition for total yield of polysaccharide was NaNO3 3.5 g/L, renewal rate 27%, renewal period 2.91 days. The optimal condition for polysaccharide output rate was NaNO3 0.5 g/L, renewal rate 5%, renewal period 7 days. With the optimal renewal regime, the maximal total recovery yields of polysaccharide achieved at 29.4 g, which was 1.57 times higher than that of batch cultivation. The maximum output rate of polysaccharide was 68.64 mg/L per day, which was 2.02 times higher than previous reported data. 相似文献